title: Growth hormone and Klotho.
abstract: Acromegaly is characterized by excessively high GH and IGF1 levels. Recent data suggest that soluble Klotho (sKlotho) is also elevated in patients with active acromegaly. sKlotho decreases towards normal following removal of the GH-producing pituitary adenoma. The Klotho gene was identified in mice following its accidental disruption by ectopic DNA. It is an ageing suppressor gene of restricted expression (mainly in kidneys, brain, and parathyroid and pituitary glands) encoding a transmembrane protein, mKlotho. mKlotho serves as a co-receptor in fibroblast growth factor 23 (FGF23) signalling. FGF23 promotes urinary phosphate excretion and inhibits the synthesis of calcitriol. The ectodomain of mKlotho is enzymatically released to result in a humoral factor, sKlotho, which exerts systemic effects (on ion channels and signalling pathways), possibly by working as an enzyme that modifies glycans of cell surface glycoproteins. GH enhances renal phosphate reabsorption and calcitriol production, i.e. exerts effects in the proximal tubule opposing those attributed to mKlotho, and attenuates calciuria in the distal tubule similar to sKlotho. sKlotho can be measured in extracellular fluids (serum, urine and cerebrospinal fluid (CSF)) by an ELISA. In line with predominant expression of Klotho in kidneys and choroid plexus, concentrations of sKlotho are particularly high in urine and CSF. Determination of sKlotho in serum and urine (both presumably reflecting GH action on the kidneys) could be used as a supplementary tool in the diagnosis and follow-up of patients with acromegaly. The question arises whether GH exerts selected actions via modifying activities of Klotho.
authors.affiliation: Division of Endocrinology and Diabetology, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland Department of Neurosurgery, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zurich, Switzerland Division of Endocrinology and Diabetology, Kantonsspital St Gallen, 9007 St Gallen, Switzerland Department of Neurosurgery, Clinic Hirslanden, Witellikerstrasse 40, 8032 Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.forename: Marian C
authors.initials: MC
authors.lastname: Neidert
authors.forename: Oliver
authors.initials: O
authors.lastname: Tschopp
authors.forename: Lisa
authors.initials: L
authors.lastname: Sze
authors.forename: René L
authors.initials: RL
authors.lastname: Bernays
mesh_terms: D000172:Acromegaly / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000652:urine; D004195:Disease Models, Animal; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase / Q000502:physiology*; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D000090265:Klotho Proteins; D051379:Mice; D015398:Signal Transduction / Q000502:physiology
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D000089703:Fibroblast Growth Factor-23; D013006:Growth Hormone; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium
keywords: FGF23; IGF1; Klotho; acromegaly; growth hormone